Solution structure of human calcitonin gene-related peptide by proton NMR and distance geometry with restrained molecular dynamics
| Autor: | Iain D. Campbell, Timothy S. Harvey, Alexander L. Breeze, Renzo Bazzo |
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| Rok vydání: | 1991 |
| Předmět: | |
| Zdroj: | Biochemistry. 30:575-582 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | The structure of human calcitonin gene-related peptide 1 (hCGRP-1) has been determined by {sup 1}H NMR in a mixed-solvent system of 50{percent} trifluoroethanol/50{percent} H{sub 2}O at pH 3.7 and 27 {degree}C. Complete resonance assignment was achieved by using two-dimensional methods. Distance restraints for structure calculations were obtained by semiquantitative analysis of intra- and interresidue nuclear Overhauser effects; in addition, stereospecific or {chi}{sup 1} rotamer assignments were obtained for certain side chains. Structures were generated from the distance restraints by distance geometry, followed by refinement using molecular dynamics, and were compared with experimental NH-C{alpha}H coupling constants and amide hydrogen exchange data. The structure of hCGRP-1 in this solvent comprises an amino-terminal disulfide-bonded loop (residues 2-7) leading into a well-defined {alpha}-helix between residues 8 and 18; thereafter, the structure is predominantly disordered, although there are indications of a preference for a turn-type conformation between residues 19 and 21. Comparison of spectra for the homologous hCGRP-2 with those of hCGRP-1 indicates that the conformations of these two forms are essentially identical. |
| Databáze: | OpenAIRE |
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